A Multimodal Neuroimaging Study of Brain Activation Patterns Under Ketamine

• ClinicalTrials.gov Identifier: NCT03609190
• Recruitment Status: Completed
• First Posted: August 1, 2018
• Last Update Posted: March 20, 2019
• Sponsor: Psychiatric University Hospital, Zurich
• Information provided by (Responsible Party): Milan Scheidegger, Psychiatric University Hospital, Zurich

Tracking Information

• First Submitted Date: July 13, 2018
• First Posted Date: August 1, 2018
• Last Update Posted Date: March 20, 2019
• Actual Study Start Date: January 2015
• Actual Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 24, 2018)

• Change in functional reactivity to emotional stimuli [ Time Frame: Change from baseline to 24h-post infusion ]
  fMRI BOLD
• Change in glutamate concentrations in prefrontal cortex [ Time Frame: Change from baseline to 24h-post infusion ]
  1H-MRS
• Change in resting-state functional connectivity [ Time Frame: Change from baseline to 24h-post infusion ]
  rsfMRI

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Multimodal Neuroimaging Study of Brain Activation Patterns Under Ketamine
• Official Title: Brain Activation Patterns Under Emotional and Neurochemic Stimulation With Ketamine: A Multimodal Neuroimaging Study

Brief Summary

The aim of the project is to establish a multimodal imaging approach for the investigation of the neural mechanisms underlying neuroreceptor regulation, glutamatergic metabolism and brain function that are of particular relevance for major depressive disorder (MDD) and that can be translated into clinical applications.

There is growing evidence for imbalance with regard to glutamatergic neurotransmission in stress-related affective disorders. Further support for the hypothesis that dysfunctional glutamatergic signaling underlies major depressive disorder, and indeed that its reversal constitutes a potential efficacious mechanism of action, is provided by the evidence that pharmacological compounds active at the N-methyl-D-aspartate (NMDA) ionotropic glutamate receptor such as ketamine exert rapid antidepressant effects. As a tool compound ketamine enables the safe investigation of the brain region-specific effects of NMDA receptor antagonism in terms of glutamatergic neurotransmission, brain function and the association of these neural changes with emotional state, thereby allowing for increased understanding of the therapeutic mechanism of action.

The possibility to simultaneously study brain perfusion (arterial spin labeling), functional brain activity (fMRI) and connectivity (resting state fMRI), neurometabolism (proton magnetic resonance spectroscopy) and metabotropic glutamate receptor densities (positron emission tomography) will unravel their functional interplay in the mechanisms underlying the regulation of mood and cognition. Combining those imaging modalities with treatment interventions in healthy subjects and depressed patients, this project aims at providing insight into the neuropharmacological effects of ketamine and its antidepressant properties.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Basic Science
• Condition: Major Depressive Disorder

Intervention

• Drug: Ketamine
  i.v. infusion of 0.25 mg/kg S-ketamine over 40 min
• Drug: Placebo
  i.v. infusion of NaCl over 40 min

Study Arms

• Experimental: Ketamine
  i.v. infusion of 0.25 mg/kg S-ketamine over 40 min
  Intervention: Drug: Ketamine
• Placebo Comparator: Placebo
  i.v. infusion of NaCl over 40 min
  Intervention: Drug: Placebo

Publications *

• Herrera-Melendez A, Stippl A, Aust S, Scheidegger M, Seifritz E, Heuser-Collier I, Otte C, Bajbouj M, Grimm S, Gärtner M. Gray matter volume of rostral anterior cingulate cortex predicts rapid antidepressant response to ketamine. Eur Neuropsychopharmacol. 2021 Feb;43:63-70. doi: 10.1016/j.euroneuro.2020.11.017. Epub 2020 Dec 11.
• Gärtner M, Aust S, Bajbouj M, Fan Y, Wingenfeld K, Otte C, Heuser-Collier I, Böker H, Hättenschwiler J, Seifritz E, Grimm S, Scheidegger M. Functional connectivity between prefrontal cortex and subgenual cingulate predicts antidepressant effects of ketamine. Eur Neuropsychopharmacol. 2019 Apr;29(4):501-508. doi: 10.1016/j.euroneuro.2019.02.008. Epub 2019 Feb 26.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 19, 2019): 10
• Original Estimated Enrollment (submitted: July 24, 2018): 30
• Actual Study Completion Date: December 2018
• Actual Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• treatment resistant depressive episode
• no restrictions regarding antidepressant medication

Exclusion Criteria:

• lifetime antidepressant treatment with ketamine
• lifetime recreational use of ketamine
• cardiovascular diseases such as hypertonia, cardiac insufficiency or myocardial infarct in the past six months
• insufficiently treated anemia
• hyper- or hypothyroidism
• lifetime increased intracranial pressure or glaucoma
• chronic physical diseases
• hepatorenal dysfunction
• any relevant psychiatric or neurological comorbidity, in particular dementia, epileptic seizures (lifetime), schizophrenia (lifetime), psychosis (lifetime), or post-traumatic stress disorder (current).
• acute suicidality
• substance abuse disorders
• recent heart or head surgery
• metallic body implants
• agoraphobia
• pregnancy
• left handedness

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT03609190
• Other Study ID Numbers: E-31/2008
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Milan Scheidegger, Psychiatric University Hospital, Zurich
• Original Responsible Party: Same as current
• Current Study Sponsor: Psychiatric University Hospital, Zurich
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Psychiatric University Hospital, Zurich
• Verification Date: March 2019